Soil erosion poses significant global challenges across socioeconomic and environmental domains. This study introduces an integrated methodology for soil loss estimation and modeling soil erosion severity in the Middle Omo-Gibe River (MOGR) basin of Southern Ethiopia. The research has employed the Revised Universal Soil Loss Equation (RUSLE) model alongside geospatial techniques, farmers' perception, and field-based survey. Results indicate a mean rainfall-runoff erosivity of 855.49 MJ mm/ha/h/year and the mean soil erodibility is 0.36 Mg/ha/MJ mm in the river basin. Over half of the basin exhibits strong slope gradients, with topographic factors ranging from 0 to 72.14. The estimated mean annual soil loss is 38.38 t/ha/yr, with 42% of the basin area surpassing the accepted erosion limit (i.e., > 10 t/ha/yr). About 54% of sub-watersheds in the river basin exhibit high to very severe soil loss, including ten sub-watersheds classified as extremely severe, with soil loss rates greater than 100 t/ha/yr. Additionally, the rate of soil loss calculated for the watershed agrees well with the results of farmers' perception, the experimentation outputs of soil physico-chemical properties, and the findings of previous studies. The finding underscores a robust framework for assessing soil erosion and facilitating informed decisions for sustainable use of land resources and conservation across various river basins in Ethiopia.